An abnormality in the renin-angiotensin system has long been suggested as a primary factor in the development and maintenance of hypertension. However, to date no firm correlation has been obtained between renin or angiotensin levels and the presence or severity of hypertension. One factor which is found in hypertensive situations with a very high frequency is an elevation of blood levels of angiotensinogen. Angiotensinogen, molecular weight of 57,700, is the precursor protein of angiotensin II, molecular weight 1300, and has been found to occur in multiple forms in pooled hog serum. The formation of angiotensin II occurs in two steps. First, renin releases a decapeptide from angiotensinogen; then, a dipeptidase removes two amino acids from the decapeptide. Thus, less than 2% of the precursor protein becomes the active pressor hormone, angiotensin II. It is proposed here that the remaining 98% of angiotensinogen may have heretofore unrecognized functions. This investigation will isolate angiotensinogen from rabbit blood, enzymatically remove the angiotensin I decapeptide and test the remaining protein fragment for biological activities. A screening procedure will be developed for assaying the proportions of the various forms of angiotensinogen in animals in a variety of pathological and physiological states. The experimental methods developed in this study will be suitable for extrapolation to human studies. BIBLIOGRAPHIC REFERENCES: Affinity Chromatography of Renin Substrate. M.P. Printz, T.J. Gregory, J.A. Lewicki and J.M. Printz, Fed. Proc. (Abst.) 3111, 1975.